Nitric oxide, a simple low molecular weight gas, has been demonstrated to be an important mediator in a wide range of physiologic processes. Specifically, nitric oxide has been identified as the endothelium derived relaxing factor (EDRF), which is fundamental in the control of vascular tone and the most potent endogenous vasodilator. It is on this basis that inhaled nitric oxide is actively being investigated as a selective pulmonary vasodilator in neonates and adults with illnesses complicated by hypoxia or thromboxane induced pulmonary hypertension (1,2 ). Despite this interest in exogenously administered nitric oxide, little is known about endogenous nitric oxide metabolism or its possible relationship to pulmonary hypertension of the newborn. Preliminary studies of neonatal patients with persistent pulmonary hypertension receiving inhaled nitric oxide found improved oxygenation and survival without ECMO (1,9). To date however, little is known about endogenous nitric oxide production or the metabolism of its immediate precursor (arginine) in human newborns. Therefore, based on available evidence, it is reasonable to hypothesize that alteration of endogenous nitric oxide production plays a pathogenic role in persistent pulmonary hypertension of the newborn, and that increasing arginine availability (by providing an L-arginine infusion) may be able to increase endogenous nitric oxide production in infants with PPHN. Performing these studies will provide additional insights into the pathogenesis of PPHN, and may be a beginning step toward providing a new alternative or adjunctive therapeutic strategy in the treatment of this disease.